NLRP3 Gene Polymorphisms in Rheumatoid Arthritis and Primary Sjogren’s Syndrome Patients

Abstract

Aim: The activation of NLRP3 inflammasome leads to the stimulation of cytokines and is significantly involved in the pathogenesis and progression of autoimmune diseases. The purpose of this study is to examine the associations of NLRP3 gene polymorphisms with rheumatoid arthritis (RA) and primary Sjogren’s syndrome (SS) patients. Methods: A total of 239 patients with RA, 285 patients with primary SS, and 170 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells, and gene polymorphisms were genotyped through the TaqMan assay. Antinuclear antibody (ANA), anti-Ro, and anti-CCP antibodies were detected using immunofluorescence immunoassay. Results: The T allele of rs4612666 CT elevated the susceptibility to RA disease. The RF titer during diagnosis of RA was significantly high in RA patients with the A allele of rs12079994 G/A polymorphism. The titer of anti-CCP during diagnosis of RA was high in the absence of the C allele of rs10754558 C/G polymorphisms in RA patients. Antinuclear antibody and anti-CCP were positively associated with the A allele of rs12079994 G/A polymorphism in primary SS. The C allele of rs4612666 C/T was negatively associated with ANA in primary SS. Conclusions: The results have shown that NLRP3 gene polymorphisms may play a role in the pathogenesis of RA and primary SS.

The role of NLRP3 and CARD8 polymorphisms in the risk of rheumatoid arthritis: A meta‐analysis of genetic association studies

“…Among them, five studies were excluded as they contained no information on polymorphism. Ultimately, 10 articles satisfied the inclusion criteria 8–17 (Figure 1). We independently reviewed these studies because one of the publications had information on two different groups 15 .…”

“…Although several studies have linked various NLRP3 and CARD8 polymorphisms to RA susceptibility, not all polymorphisms have shown a significant association. [8][9][10][11][12][13][14][15][16][17] A meta-analysis is a powerful method for combining the results of many studies, which may provide more accurate estimates of the strength of the link between genetic variants and disease susceptibility. 18 In this study, we performed a meta-analysis to investigate the association between functional NLRP3 and CARD8 polymorphisms and susceptibility to RA.…”

“…Genetic association studies have investigated the link between NLRP3 and CARD8 polymorphisms and susceptibility to RA. Although several studies have linked various NLRP3 and CARD8 polymorphisms to RA susceptibility, not all polymorphisms have shown a significant association 8–17 …”

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review

“…Nucleotide polymorphisms occur within the regulatory region of cytokine genes, and some are associated with an altered rate of gene expression. The NLRP3 inflammasome gene polymorphisms contribute to susceptibility, disease activity, or disease severity in RA [ 98 , 99 , 100 , 101 ]. The genetic variants of the NLRP3 inflammasome can also affect the therapeutic response to TNF-α inhibitors in RA patients [ 102 , 103 , 104 ].…”

Potential mechanisms and drug prediction of Rheumatoid Arthritis and primary Sjögren’s Syndrome: A public databases-based study

“…This makes it common for patients suffering from pSS to be misdiagnosed, underdiagnosed, or diagnosed too late in their illness [ 9 ]. Despite their genomic similarity, RA and pSS differ phenotypically, making it essential to gain insight into the biomarkers and pathways related to them at the transcriptomic level [ 10 ]. However, most previous studies are related to secondary Sjögren’s syndrome in RA, and few articles have reported on the pathogenesis of the co-occurrence of RA and pSS [ 11 ].…”